Microneedles Next Generation of Drug Delivery JUVIC Biotech

Microneedles: Next Generation of Drug Delivery JUVIC Biotech. Inc. Yonsei University (South Korea) Shayan F. Lahiji Shayan@yonsei. ac. kr Professor Hyungil Jung Hijung@yonsei. ac. kr

Routes of Administration Oral Delivery Implantation Inhalation Injection Transdermal

Microneedle A micro dimensioned needle Insulin needle (33 Guage) Microneedle and insulin needle

Types of Microneedle

Types of Microneedle Dissolving Microneedle Hollow Microneedle Solid Microneedle Coated Microneedle

Hollow Microneedle

Hollow Microneedle

Blood Extraction

Hollow Microneedle Drug Delivery Tower Microneedl e 31 G Hypodermic needle

Sub retinal Drug Delivery

Dissolving Microneedle A dissolving microneedle (DMN) is a micro-sized needle made of biodegradable polymer that encapsulates pharmaceuticals within a matrix and releases the drugs after skin insertion via dissolving of the polymeric compound. Permeation Dissolve Active compound absorbed skin tissue Dissolving microneedle: minimally invasive Traditional needle: Pain!

Potential of Dissolving Microneedle Dissolving microneedle is a novel drug delivery tool. 0 Chemical drug Biomedicine Cosmetics

Potential of Dissolving Microneedle Since 1990 s, various dissolving microneedle fabrication and delivery methods were developed. However, only few of traditional dissolving microneedles were commercialized and that was only in cosmetics (not in biomedicine).

Belief in dissolving microneedle Dissolving Microneedle Patch Microneedle Application Active Compound Delivery SKIN

Hidden Truth of the dissolving microneedle The essential of drug delivery is to deliver i) any drug, in ii) active form, with iii) require dose and iv) complete delivery. Key factors of dissolving microneedle Active drug Denatured drug Any Drug? Drug activity? Enough-dose? Complete Delivery?

Traditional dissolving microneedle developing process Drug solution Drug Polymer solution Drug solution Shaping technique Polymer-drug solution ① ② Patch system Microneedle fabrication ③ Patch application ④ Solvent Micromolding Drawing DAB

Lipophilic Drug Loading Any Drug? Innovative polymer system Lipophilic Drug Loading

Activity Improvement Drug activity? Enough-dose? Insulin x 300 !! Direct & High dose powder loaded DMN Highly concentrated powder loading Maximizing the amount of drug loaded in DMN Ultra-high activity of bio-drug

Polymers used as backbone materials CMC: Carboxymethylcellulose (sodium salt) Cellulose derivatives with carboxymethyl groups (-CH 2 -COOH) bound to some of the hydroxyl groups of the glucopyranose monomers Type Low viscosity Medium viscosity High viscosity Uses Viscosity modifier Thickener Emulsion stabilizer Detergent, Food additive, toothpaste, Pharmaceutical, Implantation US-FDA approved for medical use

Polymers used as backbone materials PVP: Polyvinylpyrrolidone Water-soluble polymer made from the monomer N-vinylpyrrolidone Type 2, 500 to 2, 500, 000 dalton Uses Binder of pharmaceutical tablet Stabilizer Emulsifier Membrane formation Thickener Disinfectant properties with iodine (povidone-iodine) US-FDA approved for medical use

Polymers used as backbone materials HA: Hyaluronic Acid (sodium salt) Anionic, nonsulfated glycosaminoglycan of connective, epithelial and neural tissue Type 5, 000 to 20, 000 dalton Uses Wound repair (early inflammation promoter) Skin structure (ECM: extra cellular matrix) Treat osteoarthritis US-FDA approved for medical use

Novel Fabrication Methods Fabrication Method? Activity? Through C-Method we can fabricate Various forms of Dissolving Microneedles and ensure it maintains its activity. Patented by Ju. Vic Biotech Co.

Novel Fabrication Methods Fastest available Fabrication Method Within 5 minutes Dose control Temperature control

Novel Fabrication Methods

Novel Fabrication Methods Droplet-born Air Blowing Base preparation Droplet dispensing Droplet contact Microneedle length control Air blowing and separation

Novel Fabrication Methods

Limitation of incomplete patch administration Complete Delivery? 11. 0 N Micro-lancer Dissolving microneedle delivery system 16. 4 N

Limitation of incomplete patch administration

Limitation of incomplete patch administration Hair-less skin (Patch) Microlancer Hairy skin (Patch) Microlancer Patch

JUVIC - Innovative technologies using microneedles - Innovation Company for Microneedle - Total solution using microneedle for transdermal delivery Summary Micro-lancer Implantable Shooter micro-capsule Innovative DMN on micro-pillar polymer system (IPS) Traditional DMN patch Precision DMN patch Transdermal delivery of compounds by attaching adhesive patch with DMN array Precision delivery of drugs by attaching adhesive patch with DMN array Shooting DMNs into skin by using a convenient micro-lancer applicator Implanting micro-capsule with DMN into skin to deliver powder drugs Perfect penetration and delivery of DMNs fabricated on micro-pillars Loading lipophilic drugs by using amphipathic polymer system Cosmetics Bio-pharmacy Vaccines Alopecia Arthritis Cosmetic filler Bio-pharmacy Alopecia Arthritis Lipophilic drugs Alopecia Arthritis Applications Cosmetics JUVIC Biotech. Inc.

JUVIC – Practical products Cosmetics Non-patch anti-wrinkle cosmetics Precision DMN patch Micro-lancer Shooter Retinyl retinoate Whitening cosmetics Precision DMN patch Innovative polymer system (IPS) Alopecia treatment cosmetics Micro-lancer Shooter Implantable micro-capsule Corticosteroid Vitamin C derivative Long-lasting cosmetic filler Precision DMN patch DMN on micro-pillar High molecular weight HA Biomedicine High dose powder drug delivery Precision DMN patch Implantable micro-capsule Lipophilic drug delivery Precision DMN patch Innovative polymer system (IPS)

JUVIC – Previous products AA-DMN RR-DMN - Anti-wrinkle dissolving microneedle patch Before application After 12 weeks Photographs of subject wrinkles at 0 weeks and 12 weeks

JUVIC – Previous products

Acknowledgement Professor Hyungil Jung Nano-biotechnology Lab members: Manita Dangol Changyeol Lee Sunguk Lee Huisuk Yang Suyong Kim Mingyu Jang Chisong Lee Inyong Heo

Thank You! Shayan F. Lahiji Shayan@yonsei. ac. kr Professor Hyungil Jung Hijung@yonsei. ac. kr